Analysis Tools
immune system
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• germinal center B cell populations exhibit a greater frequency of live B cells and reduced death of B cells indicating enhanced survival of germinal center B cells
• treatment with a selective PI3KD inhibitor reduces both the viability of B cells in vitro
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• follicular B cells stimulated with lipopolysaccharide (LPS) exhibit increased proliferation
• B cell activating factor (BAFF) increases B cell proliferation which is not seen in wild-type B cells
• treatment with a selective PI3KD inhibitor reduces the proliferation of B cells in vitro
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• increase in spleen cellularity
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces splenic cellularity
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• mice exhibit a greater number of and altered populations of CD93+ transitional B cells, including more T1 cells, indicating a partial developmental block of B cells
• however, frequency of splenic B cells is similar to wild-type
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the number of activated CD4+ T cells
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• within the NP+ germinal center B cell compartment, a lower frequency of IgG1+ cells is seen indicating inefficient class-switched antigen-specific B cell responses to immunization
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• mice exhibit a greater number of and altered populations of CD93+ transitional B cells, including more T1 cells
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• perivascular and peribronchial lymphoid aggregates in the lungs
• 1-year-old mice exhibit lymphocytic infiltration in multiple organs
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• mice exhibit more germinal center B cells in the lymph nodes, the spleen, and in Peyer's patches
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• mice exhibit more peritoneal B-1a cells
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• mice exhibit more splenic CD138+ plasma cells
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the frequency and number of plasma cells
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• although 2-month-old mice show a relatively normal number of follicular helper T cells in the peripheral lymph nodes, the frequency and number of these cells are increased in both the lymph nodes and spleen with age
• greater frequency of PD-1+CXCR5+CD4+ T cells in the spleen, including both Foxp3- follicular helper T cells and Foxp3+ follicular helper regulatory T cells
• however, the ratio of follicular helper T cells to follicular helper regulatory T cells is normal
• BCL-6lo pre-follicular helper T cell and BCL-6hi germinal center follicular helper T cell populations are expanded
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the number of T follicular helper cells
• Peyers patches and mesenteric lymph nodes show a greater number of T follicular helper cells
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• lower frequency of activated CD4+ T cells in the spleen and peripheral lymph nodes
• however, frequency of CD4+ T cells is similar to wild-type
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• mice exhibit fewer circulating white blood cells at 4 months of age
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• lower frequency of naive CD4+ T cells in the spleen and peripheral lymph nodes
• by 1 year of age, mice have almost no CD62+CD44lo naive CD4+ T cells
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• mice show a reduction in the abundance of IgD+ naive B cells with age
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• mice exhibit an increase in plasmablasts
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the frequency and number of plasmablasts
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• splenic follicular B cells show greater responsiveness to autologous fecal microbiome extracts and lower threshold for the expression of activation markers in response to autologous fecal microbiome extracts, as well as to LPS
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• mice exhibit a greater abundance of free fecal IgA and a greater frequency of fecal IgA-coated bacteria
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• NP-specific IgG1 levels are lower in serum despite greater total IgG1, probably due to increased abundance of activated B and plasma cells
• however, the ratio of high-affinity antibodies to NP4 to total antibodies to NP20 is normal
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• total IgG in serum is increased
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the abundance of total IgG
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• total IgM in serum is increased
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• mice exhibit expanded activated lymphocyte populations
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• mice exhibit altered homeostasis of gut-associated lymphoid tissue with increased IgA-coated fecal bacteria
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• Peyers patches show increased cellularity and a greater number of T follicular helper cells and germinal center B cells
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• increase in germinal center B cell number
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• mesenteric lymph nodes show increased cellularity and a greater number of T follicular helper cells and germinal center B cells
• mesenteric lymph nodes display a greater abundance of germinal centers scattered throughout the internal medullary area than in the cortical region
• mesenteric lymph nodes show disorganization of germinal centers, with poor demarcation of dark zone and light zone areas and infiltration of PD-1+ T follicular helper cells into the dark zone
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• the resting lymph nodes have expanded germinal center areas that fill the follicular dendritic cell networks and almost all follicular dendritic cell areas are occupied with BCL-6+ germinal centers which is not seen in resting lymph nodes of wild-type mice
• germinal centers from both resting lymph nodes and draining lymph nodes show altered organization, with more invasion of the dark zone by follicular helper T cells
• size of draining lymph node germinal centers varies
• reduction in the dark zone and a greater frequency of light zone NP+ germinal center B cells and poor demarcation of light zone and dark zone area
• greater frequency of Foxp3+ regulatory T cells and follicular helper T cells
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• resting lymph nodes exhibit greater cellularity
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• increase in number and size of isolated lymphoid follicles in the small intestines indicating gastrointestinal lymphoid hyperplasia
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• mice immunized with T cell-dependent antigen NP-OVA at 4 months of age do not show an increase in the frequency of follicular helper T cells or germinal center B cells in the draining lymph nodes as is seen in controls indicating defective T cell-dependent humoral responses
• however, 2-month-old mice show a similar response as wild-type mice
• frequency and number of antigen-binding (NP+) germinal center B cells is lower and the ratio of NP+ antigen-specific germinal center B cells to NP- germinal center cells is lower
• by 1 year of age, many mice have very few NP-specific germinal center B cells after immunization
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• mice exhibit a higher frequency of IgG2a/b that bind fecal bacteria in the serum, indicative of greater systemic responses to gut commensals
• mice show more binding of IgG to A. muciniphila, but not the control Lactobacillus reuteri
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• increase in IgG and IgM anti-nuclear antibodies in the serum
• IgM and IgG antibodies directed against approximately 50 autoantibodies are increased
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• mice show an increase in innate reactivity to commensal-derived products
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• mice show an increase in antigen-specific reactivity to commensal-derived products
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hematopoietic system
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• germinal center B cell populations exhibit a greater frequency of live B cells and reduced death of B cells indicating enhanced survival of germinal center B cells
• treatment with a selective PI3KD inhibitor reduces both the viability of B cells in vitro
|
|
• follicular B cells stimulated with lipopolysaccharide (LPS) exhibit increased proliferation
• B cell activating factor (BAFF) increases B cell proliferation which is not seen in wild-type B cells
• treatment with a selective PI3KD inhibitor reduces the proliferation of B cells in vitro
|
|
• increase in spleen cellularity
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces splenic cellularity
|
|
• mice exhibit a greater number of and altered populations of CD93+ transitional B cells, including more T1 cells, indicating a partial developmental block of B cells
• however, frequency of splenic B cells is similar to wild-type
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the number of activated CD4+ T cells
|
|
• within the NP+ germinal center B cell compartment, a lower frequency of IgG1+ cells is seen indicating inefficient class-switched antigen-specific B cell responses to immunization
|
|
• mice exhibit a greater number of and altered populations of CD93+ transitional B cells, including more T1 cells
|
|
• perivascular and peribronchial lymphoid aggregates in the lungs
• 1-year-old mice exhibit lymphocytic infiltration in multiple organs
|
|
• mice exhibit more germinal center B cells in the lymph nodes, the spleen, and in Peyer's patches
|
|
• mice exhibit more peritoneal B-1a cells
|
|
• mice exhibit more splenic CD138+ plasma cells
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the frequency and number of plasma cells
|
|
• although 2-month-old mice show a relatively normal number of follicular helper T cells in the peripheral lymph nodes, the frequency and number of these cells are increased in both the lymph nodes and spleen with age
• greater frequency of PD-1+CXCR5+CD4+ T cells in the spleen, including both Foxp3- follicular helper T cells and Foxp3+ follicular helper regulatory T cells
• however, the ratio of follicular helper T cells to follicular helper regulatory T cells is normal
• BCL-6lo pre-follicular helper T cell and BCL-6hi germinal center follicular helper T cell populations are expanded
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the number of T follicular helper cells
• Peyers patches and mesenteric lymph nodes show a greater number of T follicular helper cells
|
|
• lower frequency of activated CD4+ T cells in the spleen and peripheral lymph nodes
• however, frequency of CD4+ T cells is similar to wild-type
|
|
• mice exhibit fewer circulating white blood cells at 4 months of age
|
|
• lower frequency of naive CD4+ T cells in the spleen and peripheral lymph nodes
• by 1 year of age, mice have almost no CD62+CD44lo naive CD4+ T cells
|
|
• mice show a reduction in the abundance of IgD+ naive B cells with age
|
|
• mice exhibit an increase in plasmablasts
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the frequency and number of plasmablasts
|
|
• splenic follicular B cells show greater responsiveness to autologous fecal microbiome extracts and lower threshold for the expression of activation markers in response to autologous fecal microbiome extracts, as well as to LPS
|
|
• mice exhibit a greater abundance of free fecal IgA and a greater frequency of fecal IgA-coated bacteria
|
|
• NP-specific IgG1 levels are lower in serum despite greater total IgG1, probably due to increased abundance of activated B and plasma cells
• however, the ratio of high-affinity antibodies to NP4 to total antibodies to NP20 is normal
|
|
• total IgG in serum is increased
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces the abundance of total IgG
|
|
• total IgM in serum is increased
|
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• mice exhibit expanded activated lymphocyte populations
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cellular
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• germinal center B cell populations exhibit a greater frequency of live B cells and reduced death of B cells indicating enhanced survival of germinal center B cells
• treatment with a selective PI3KD inhibitor reduces both the viability of B cells in vitro
|
|
• follicular B cells stimulated with lipopolysaccharide (LPS) exhibit increased proliferation
• B cell activating factor (BAFF) increases B cell proliferation which is not seen in wild-type B cells
• treatment with a selective PI3KD inhibitor reduces the proliferation of B cells in vitro
|
digestive/alimentary system
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• increase in number and size of isolated lymphoid follicles in the small intestines
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• overall community structure of the microbiota is not different from wild-type mice, however phylogenetic diversity, reflecting the richness in number and phylogenetic distribution of taxa within a single community, is lower
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growth/size/body
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• increase in spleen cellularity
• treatment of mice with a cocktail of antibiotics for 6 weeks, beginning at weaning, reduces splenic cellularity
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respiratory system
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• perivascular and peribronchial lymphoid aggregates in the lungs indicative of recurrent respiratory infections
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| immunodeficiency 14 | DOID:0111936 |
OMIM:615513 |
J:282486 | |
